Techniques for controlling end-tidal partial pressures of carbon dioxide, oxygen and other gases are gaining increasing importance for a variety of research, diagnostic and medicinal purposes. Methods for controlling end tidal pressures of gases have gained particular importance as a means for manipulating arterial levels of carbon dioxide (and also oxygen), for example to provide a controlled vasoactive stimulus to enable the measurement of cerebrovascular reactivity (CVR) e.g. by MRI.
Conventional methods of manipulating arterial carbon dioxide levels such as breath holding, hyperventilation and inhalation of fixed concentration of carbon dioxide balanced with medical air or oxygen are deficient in their ability to rapidly and accurately attain targeted arterial carbon dioxide partial pressures for the purposes of routinely measuring vascular reactivity in a rapid and reliable manner.
The end-tidal partial pressures of gases are determined by the gases inspired into the lungs, the mixed venous partial pressures of gases in the pulmonary circulation, and the exchange of gases between the alveolar space and the blood in transit through the pulmonary capillaries. Changes in the end-tidal partial pressures of gases are reflected in the pulmonary end-capillary partial pressures of gases, which in turn flow into the arterial circulation. The gases in the mixed-venous blood are determined by the arterial inflow of gases to the tissues and the exchange of gases between the tissue stores and the blood, while the blood is in transit through the tissue capillary beds.
In the simplest approaches, manipulation of the end-tidal partial pressures of gases has been attempted with fixed changes to the composition of the inspired gas. However, without any additional intervention, the end-tidal partial pressures of gases vary slowly and irregularly as exchange occurs at the lungs and tissues. Furthermore, the ventilatory response to perturbations in the end-tidal partial pressures of gases is generally unpredictable and potentially unstable. Often, the ventilatory response acts to restore the condition of the blood to homeostatic norms. Therefore, any changes in the end-tidal partial pressures of gases are immediately challenged by a disruptive response in the alveolar ventilation. Consequently, fixed changes in the inspired gas composition provoke only slow, irregular, and transient changes in blood gas partial pressures.
In more complex approaches, manipulation of the end-tidal partial pressures of gases has been attempted with negative feedback control. This approach continuously varies the composition of the inspired gas so as to minimize error between measured and desired end-tidal partial pressures of gases. Technically, such systems suffer from the same limitations as all negative feedback control systems—an inherent trade-off between response time and stability. For example, to generate a transition (e.g. a 10 mm. Hg increase) in PetCO2 for imaging vascular reactivity of the heart (e.g. by MRI) rapid transition times can be commercially vital but augmenting transition time cannot be done at the expense of stability. Stability may also be affected by irregular breathing in response to exercise, in response to positioning of a subject on a medical examination table or as a result of stresses arising during the course of a diagnostic procedure in which control of blood gas concentration is used as a stimulus. Notably, elevating the partial pressure of CO2 (and to some extent oxygen) causes hyperventilation which in turn affects stability. Consequently, there is a need to overcome previous limitations in end-tidal gas control, allowing for more precise and rapid execution of end tidal gas targeting sequences in a wide range of subjects and environments.